Inhaled Nitric Oxide Reverses the Increase in Pulmonary Vascular Resistance Induced by Permissive Hypercapnia in Patients with Acute Respiratory Distress Syndrome

Abstract

The aim of this prospective study was to determine if inhaled nitric oxide (NO) would reverse the increase in pulmonary arterial pressures and in pulmonary vascular resistance induced by acute permissive hypercapnia in patients with acute respiratory distress syndrome. In 11 critically ill patients (mean age 59 +/- 22 yr) with acute respiratory distress syndrome (Murray Score > or = 2.5), the lungs were mechanically ventilated with NO 2 ppm during both normocapnic and hypercapnic conditions. Four phases were studied: normocapnia (arterial carbon dioxide tension 38 +/- 6 mmHg, tidal volume (655 +/- 132 ml); normocapnia plus inhaled NO 2 ppm; hypercapnia (arterial carbon dioxide tension 65 +/- 15 mmHg, tidal volume 330 +/- 93 ml); and hypercapnia plus inhaled NO 2 ppm. Continuous recordings were made of heart rate, arterial pressure, pulmonary artery pressure, tracheal pressure, and tidal volume (by pneumotachograph). At the end of each condition, arterial pressure, pulmonary artery pressure, cardiac filling pressures, and cardiac output were measured. Simultaneous arterial and mixed venous blood samples were obtained to measure arterial oxygen tension, arterial carbon dioxide tension, mixed venous oxygen tension, arterial hemoglobin oxygen saturation, mixed venous hemoglobin oxygen saturation, pH, and blood hemoglobin and methemoglobin concentrations (by hemoximeter). In addition, plasma concentrations of catecholamines were measured with a radioenzymatic assay. In 5 patients, end-tidal carbon dioxide tension was measured with a nonaspirative infrared capnometer. Calculations were made of pulmonary vascular resistance index, systemic vascular resistance index, true pulmonary shunt, and alveolar dead space. During hypercapnia, NO decreased pulmonary vascular resistance index from 525 +/- 223 to 393 +/- 142 dyn.s.cm-5.m-2 (P < 0.01), a value similar to that measured in normocapnic conditions (391 +/- 122 dyn.s.cm-5.m-2). It also reduced mean pulmonary artery pressure from 40 +/- 9 to 35 +/- 8 mmHg (P < 0.01). NO increased arterial oxygen tension (inspired oxygen fraction 1) from 184 +/- 67 to 270 +/- 87 mmHg during normocapnia and from 189 +/- 73 to 258 +/- 101 mmHg during hypercapnia (P < 0.01). NO decreased true pulmonary shunt during normocapnia (from 34 +/- 3% to 28 +/- 4%, P < 0.001) but had no significant effect on it during hypercapnia (39 +/- 7% vs. 38 +/- 8.5%). In five patients, NO resulted in a decrease in alveolar dead space from 34 +/- 7% to 28 +/- 10% in normocapnic conditions and from 30 +/- 9% to 22 +/- 10% in hypercapnic conditions (P < 0.05). Inhaled NO completely reversed the increase in pulmonary vascular resistance index induced by acute permissive hypercapnia. It only partially reduced the pulmonary hypertension induced by acute permissive hypercapnia, probably because the flow component of the increase in pulmonary pressure (i.e., the increase in cardiac output) was not reduced by inhaled NO. A significant increase in arterial oxygenation after NO administration was observed during normocapnic and hypercapnic conditions. A ventilation strategy combining permissive hypercapnia and inhaled NO may reduce the potentially deleterious effects that permissive hypercapnia alone has on lung parenchyma and pulmonary circulation.